Individual changes in neurocognitive functioning and health-related quality of life in patients with brain oligometastases treated with stereotactic radiotherapy.

BACKGROUND: Recently, it has been shown that at group level, patients with limited brain metastases treated with stereotactic radiotherapy (SRT) maintain their pre-treatment levels of neurocognitive functioning (NCF) and health-related quality of life (HRQoL). The aim of this study was to evaluate NCF and HRQoL changes over time at the individual patient level. METHODS: NCF (seven domains assessed with a standardized test battery) and HRQoL (eight predetermined scales assessed with the EORTC QLQ-C30 and BN20 questionnaires) were measured prior to SRT and at 3 and/or 6 months follow-up. Changes in NCF and HRQoL were evaluated at (1) a domain/scale level and (2) patient level. RESULTS: A total of 55 patients were examined, of which the majority showed stable NCF 3 months after SRT, on both the domain level (78-100% of patients) and patient level (67% of patients). This was different for HRQoL, where deterioration in the different scales was observed in 12-61% of patients, stable scores in 20-71%, and improvement in 16-40%, 3 months after SRT. At patient level, most patients (64%) showed both improvement and deterioration in different HRQoL scales. Results were similar between 3 and 6 months after SRT. CONCLUSION: In line with results at group level, most brain oligometastases patients with ≥ 6 months follow-up and treated with SRT maintained their pre-treatment level of NCF during this period. By contrast, changes in HRQoL scores differed considerably at domain and patient level, despite stable HRQoL scores at group level.

Neurocognitive functioning and health-related quality of life in patients treated with stereotactic radiotherapy for brain metastases: a prospective study.

BACKGROUND: Stereotactic radiotherapy (SRT) is expected to have a less detrimental effect on neurocognitive functioning and health-related quality of life (HRQoL) than whole-brain radiotherapy. To evaluate the impact of brain metastases and SRT on neurocognitive functioning and HRQoL, we performed a prospective study. METHODS: Neurocognitive functioning and HRQoL of 97 patients with brain metastases were measured before SRT and 1, 3, and 6 months after SRT. Seven cognitive domains were assessed. HRQoL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and BN20 questionnaires. Neurocognitive functioning and HRQoL over time were analyzed with linear mixed models and stratified for baseline Karnofsky performance status (KPS), total metastatic volume, and systemic disease. RESULTS: Median overall survival of patients was 7.7 months. Before SRT, neurocognitive domain and HRQoL scores were lower in patients than in healthy controls. At group level, patients worsened in physical functioning and fatigue at 6 months, while other outcome parameters of HRQoL and cognition remained stable. KPS < 90 and tumor volume >12.6 cm(3) were both associated with worse information processing speed and lower HRQoL scores over 6 months time. Intracranial tumor progression was associated with worsening of executive functioning and motor function. CONCLUSIONS: Prior to SRT, neurocognitive functioning and HRQoL are moderately impaired in patients with brain metastases. Lower baseline KPS and larger tumor volume are associated with worse functioning. Over time, SRT does not have an additional detrimental effect on neurocognitive functioning and HRQoL, suggesting that SRT may be preferred over whole-brain radiotherapy.

Pseudo-progression after stereotactic radiotherapy of brain metastases: lesion analysis using MRI cine-loops.

Stereotactic radiotherapy (SRT) of brain metastasis can lead to lesion growth caused by radiation toxicity. The pathophysiology of this so-called pseudo-progression is poorly understood. The purpose of this study was to evaluate the use of MRI cine-loops for describing the consecutive events in this radiation induced lesion growth. Ten patients were selected from our department's database that had received SRT of brain metastases and had lesion growth caused by pseudo-progression as well as at least five follow-up MRI scans. Pre- and post SRT MRI scans were co-registered and cine-loops were made using post-gadolinium 3D T1 axial slices. The ten cine loops were discussed in a joint meeting of the authors. The use of cine-loops was superior to evaluation of separate MRI scans for interpretation of events after SRT. There was a typical lesion evolution pattern in all patients with varying time course. Initially regression of the metastases was observed, followed by an enlarging area of new contrast enhancement in the surrounding brain tissue. Analysis of consecutive MRI's using cine-loops may improve understanding of pseudo-progression. It probably represents a radiation effect in brain tissue surrounding the irradiated metastasis and not enlargement of the metastasis itself.

Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review.

PURPOSE: Stereotactic radiotherapy (SRT) of brain metastases is considered effective when long-term local control is obtained. However, dose-effect data are scarce. We, therefore, performed a systematic literature search to assess the evidence concerning the relation of SRT dose and local control probability. METHODS AND MATERIALS: A search was performed for papers describing patients treated with SRT for brain metastases, published from 1990 through 2009, in the electronic databases Medline (Pubmed) and Embase. We selected only papers reporting actuarial local control probability, in which a fixed dose had been prescribed and in which the size of the metastases was given. Series with SRT as a boost after whole brain irradiation (WBI) or with SRT after surgery were excluded. From the selected papers we extracted data on dose, local control rates and necrosis rates. Biological effective doses of the linear-quadratic-cubic model, using an α/ß of 12Gy (BED(12)), were calculated and a dose-response curve was constructed. RESULTS: Eleven papers fulfilled the selection criteria for further analysis. Six-month local control rates were higher than 80% in almost all the series irrespective of dose. Twelve-month local control rates, however, varied and were higher than 80%, higher than 60% and lower than 50% with single doses of ≥21Gy, ≥18Gy and ≤15Gy, respectively, and 70% or higher with fractionated SRT (FSRT). A BED(12) of at least 40Gy was associated with a twelve-month local control rate of 70% or more. CONCLUSION: Local control after single fraction SRT is highly dependent upon dose and is high (>80%) after 21Gy or more, but low (<50%) after 15Gy or less. We conclude that SRT for brain metastases should preferably be applied with a BED(12) of at least 40Gy corresponding with a single fraction of 20Gy, two fractions of 11.6Gy or three fractions of 8.5Gy.

Relationship between volume, dose and local control in stereotactic radiosurgery of brain metastasis.

The aim of this study is to analyse the efficacy of linear accelerator stereotactic radiosurgery (SRS) on prognostic factors, local control rate and survival in patients with brain metastasis. Patients with either a single metastasis or up to 4 multiple brain metastases with a maximum tumour diameter of 40 mm for each tumour and a Karnofsky Performance Status (KPS) > or = 70 were eligible for SRS. SRS was applied to 150 lesions in 86 consecutive patients with a median age of 60 years (median 1 and mean 1.7 lesions per patient, mean KPS 86). Median overall survival was 6.2 months after SRS and 9.7 months from diagnosis of brain metastasis. Multivariate analysis revealed that a KPS of 90 or more (p = 0.009) and female sex (p = 0.003) were associated with a longer survival. Radiation dose < or = 15 Gy (p = 0.017) and KPS < 90 (p = 0.013) were independent predictors of a shorter time to local failure. Five patients showed evidence of radionecrosis with a median survival of 14.8 months. Addition of WBRT neither led to improvement of survival nor to improvement of local control. Improved local control following SRS for brain metastases was associated with KPS > or =90, a radiation dose > 15 Gy and a PTV < 13 cc. The potential of hypofractionated stereotactic radiotherapy (SRT) for brain metastases of larger volume warrants further study.